Social environment contributes to individual differences in the incidence and symptomology of a wide range of human health conditions, including depression, cancer, cardiovascular disease, cerebrovascular disease, wound healing, and neuropathic pain. Our laboratory and others have successfully recapitulated the exacerbating effects of social isolation on outcome in rodent models of these disorders; a common physiological feature of each of these conditions is increased neuroinflammation among socially isolated animals relative to socially housed animals. In turn, neuroinflammation is associated with greater physical and psychological morbidity, although the physiological link between social behavior and neuroinflammation is not known. We propose that oxytocin, a hormone that is released by social interaction, provides a protective function by suppressing the activation of microglia. The specific hypothesis tested in this proposal is that oxytocin reduces the expression of proinflammatory cytokines in the brain by suppressing microglial activation. Converging evidence of oxytocin modulation of microglia will be provided through in vivo and in vitro experiments. The data collected as part of this proposal will increase our understanding of how variation in social environment can impact health. Identification of the physiological factors underlying social influences on health could facilitate the development of therapeutic approaches that improve health measures among people with impoverished social environments.